Study of WNT974 in Combination With LGX818 and Cetuximab in Patients With BRAF-mutant Metastatic Colorectal Cancer (mCRC) and Wnt Pathway Mutations
NCT ID: NCT02278133
Last Updated: 2017-10-09
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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COMPLETED
PHASE1/PHASE2
20 participants
INTERVENTIONAL
2014-12-31
2017-06-23
Brief Summary
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The design of this study is based upon the translational and pre-clinical data that suggest that Wnt pathway signals, increased due to RNF43 mutations or RSPO fusions, cooperate with the EGFR and BRAF signals to maintain the growth of BRAFV600 CRCs. Inhibition of these signals with the triple combination of WNT974, LGX818 and cetuximab may result in anti-tumor activity.
Detailed Description
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Conditions
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Keywords
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Study Design
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NA
SINGLE_GROUP
TREATMENT
NONE
Study Groups
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WNT974, LGX818 and cetuximab combo
Phase l: Dose Escalation phase; Phase ll: SIngle group assessing the triple combination of WNT974, LGX818 and cetuximab
WNT974
LGX818
Cetuximab
Interventions
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WNT974
LGX818
Cetuximab
Eligibility Criteria
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Inclusion Criteria
* Histological or cytological confirmed metastatic colorectal cancer
* Written documentation of KRAS wild-type status and BRAFV600-mutation with RNF43 mutation and/or RSPO fusion
* Progression of disease after at least one prior standard of care regimen or intolerant to irinotecan based regimens
* Availability of a representative tumor specimen (primary or metastatic, archival or newly obtained)
* Measurable disease as per RECIST v1.1
* Eastern cooperative oncology group (ECOG) performance status ≤ 2
Exclusion Criteria
* Symptomatic brain metastasis. Patients previously treated or untreated for these conditions that are asymptomatic in the absence of corticosteroid and anti-epileptic therapy are allowed to enroll
* Current treatment with medications or consuming foods that are strong inhibitors or inducers of CYP3A4/5 or herbal medications and that cannot be discontinued at least one week prior to the start of treatment.
* Symptomatic or untreated leptomeningeal disease
* Acute or chronic pancreatitis
* Clinically significant cardiac disease
* Patients with any of the following laboratory values at Screening/baseline
* Absolute neutrophil count (ANC) \<1,500/mm3
* Platelets \< 100,000/mm3
* Hemoglobin \< 9.0 g/dL
* Serum creatinine \>1.5 x ULN or calculated or directly measured CrCl \< 50% lower limit of normal
* Serum total bilirubin \>1.5 x ULN
* AST/SGOT and/or ALT/SGPT \> 2.5 x ULN, (\> 5 x ULN if liver metastases present)
* Patients with impaired hepatic function as defined by Childs-Pugh class B or C
* Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral WNT974/LGX818
18 Years
ALL
No
Sponsors
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Array BioPharma
INDUSTRY
Responsible Party
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Principal Investigators
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Clinical Trial Call Center
Role: STUDY_DIRECTOR
Array BioPharma, Inc.
Locations
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Memorial Sloan-Kettering Cancer Center (MSKCC) MSKCC (3)
New York, New York, United States
Medical University of South Carolina Oncology Dept
Charleston, South Carolina, United States
University of Texas/MD Anderson Cancer Center Onc. Dept,
Houston, Texas, United States
University of Wisconsin / Paul P. Carbone Comp Cancer Center Univ Wisc
Madison, Wisconsin, United States
Array BioPharma Investigative Site
Parkville, Victoria, Australia
Array BioPharma Investigative Site
Leuven, , Belgium
Array BioPharma Investigative Site
Edmonton, Alberta, Canada
Array BioPharma Investigative Site
Vancouver, British Columbia, Canada
Array BioPharma Investigative Site
Toronto, Ontario, Canada
Array BioPharma Investigative Site
Bordeaux, , France
Array BioPharma Investigative Site
Marseille, , France
Array BioPharma Investigative Site
Tel Aviv, , Israel
Array BioPharma Investigative Site
Milan, MI, Italy
Array BioPharma Investigative Site
Amsterdam, , Netherlands
Array BioPharma Investigative Site
Singapore, , Singapore
Array BioPharma Investigative Site
Barcelona, Catalonia, Spain
Array BioPharma Investigative Site
L'Hospitalet de Llobregat, Catalonia, Spain
Array BioPharma Investigative Site
Madrid, , Spain
Array BioPharma Investigative Site
Madrid, , Spain
Countries
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References
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VAN Bussel MTJ, Bravenboer N, Essen HV, Snaebjornsson P, Appelman-Dijkstra NM, Schellens JH, Opdam FL. Bone Toxicity Case Report Combining Encorafenib, Cetuximab and WNT974 in a Phase I Trial. Anticancer Res. 2025 Jul;45(7):3137-3147. doi: 10.21873/anticanres.17677.
Tabernero J, Van Cutsem E, Garralda E, Tai D, De Braud F, Geva R, van Bussel MTJ, Fiorella Dotti K, Elez E, de Miguel MJ, Litwiler K, Murphy D, Edwards M, Morris VK. A Phase Ib/II Study of WNT974 + Encorafenib + Cetuximab in Patients With BRAF V600E-Mutant KRAS Wild-Type Metastatic Colorectal Cancer. Oncologist. 2023 Mar 17;28(3):230-238. doi: 10.1093/oncolo/oyad007.
Other Identifiers
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CWNT974X2102C
Identifier Type: -
Identifier Source: org_study_id